Use of intravesical valrubicin in clinical practice for treatment of nonmuscle-invasive bladder cancer, including carcinoma in situ of the bladder

Abstract

Objectives:The objective was to conduct a US multicenter, retrospective medical record study examining the effectiveness, safety, and patterns of use of valrubicin for treatment of nonmuscle-invasive bladder cancer (NMIBC) by clinicians since the 2009 reintroduction of valrubicin. Methods: Patients ≥ 18 years with NMIBC who received had one or more instillations of valrubicin (October 2009-September 2011 were eligible. The primary endpoint was eventfree survival (EFS). Safety and tolerability were also assessed. Results: The medical records of 113 patients met the inclusion criteria; 100 patients (88.5%) completed valrubicin treatment. The median age was 75 years (range 42-95 years). The median NMIBC duration was 31 months since diagnosis: 51.3% (58/113) had carcinoma in situ (CIS) alone, and 31.9% (36/113) had unspecified NMIBC. Most patients, 94.7% (107/113), had more than three valrubicin instillations and 70.8% (80/113) completed a full course. The EFS rate (95% confidence interval) was 51.6% (40.9-61.3%), 30.4% (20.4-41.1%), and 16.4% (7.9-27.5%) at 3, 6, and 12 months, respectively. Median time to an event was 3.5 (2.5-4.0) months after the first valrubicin instillation. Local adverse reactions (LARs) were experienced by 49.6% (56/113) of patients; most LARs were mild (93.6%). The most frequent LARs were hematuria, pollakiuria, micturition urgency, bladder spasm, and dysuria. In total, 4.4% (5/113) of patients discontinued valrubicin because of adverse events or LARs. Conclusions: Data from the present retrospective study are consistent with previous prospective clinical trials that demonstrated valrubicin effectiveness and tolerability for select patients with CIS, before considering cystectomy. Additional prospective studies are warranted to evaluate valrubicin safety and efficacy in the broader patient population with NMIBC.

Intravesical therapy for bladder cancer

“…Valrubicin was voluntarily removed from the market in 2002 due to manufacturing issues and was reintroduced in 2009 [82]. In its initial Phase III study, 90 patients who previously failed at least one course of BCG and had recurrent CIS were given 6 weekly instillations of 800 mg of Valrubicin.…”

The Role of Interferon in the Management of BCG Refractory Nonmuscle Invasive Bladder Cancer

“…In the pivotal trial the disease-free status at 12 months was 10%, inferior to the results reported by O'Donnell and colleagues with combination BCG plus interferon. This low event-free survival (EFS) was recently validated in a retrospective study by Cookson et al [ 17 ], where the 12-month EFS following valrubicin instillation was calculated at 16.4%. Valrubicin was seldom used during the current study period due to the low number of patients with CIS in the recurrence specimen and the fact that the medication was off the market for half of the study period (2004–2009).…”

Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with P-MAPA and systemic administration of cisplatin and doxorubicin

“…Therefore, the recommended standard of care for patients with recurrent high-grade disease after optimal BCG treatment has been to proceed with cystectomy ( 3 , 16 ). However, patients who refuse or are unfit for bladder removal face an increased risk of progression to muscleinvasive disease ( 3 , 16 ). No approved drug presenting similar or superior outcomes than BCG are available for treatment of this condition.…”